PROJECT SUMMARY Emotional distress disorders are both common (lifetime prevalence rates ranging from 18-32%) and costly (global economic cost of $1.15 trillion dollars annually). Despite an increased focus on defining the mechanisms of psychopathology within a psychobiological framework, distinct biological processes have yet to be identified specific to individual emotional distress disorders. These limitations are, in part, responsible for the current paradigm shift in research on psychopathology, embodied by the Research Domain Criteria (RDoC). RDoC has proposed a shift to focus on narrow, dimensional, psychological constructs associated with biological processes and behaviors. The limitations of the current diagnostic system also have led to the hierarchical taxonomy of psychopathology (HiTOP), evidence from which supports dividing emotional distress disorders into distress and fear clusters of disorders. Focusing on constructs that operate as risk factors across multiple emotional distress disorders could integrate these two approaches. Anxiety sensitivity (AS), or the fear of anxious arousal as likely catastrophic, and intolerance of uncertainty (IU), or maladaptive emotional arousal when confronted with potentially negative unknown events, are two such risk factors. However, to unite these two disparate approaches, it must be demonstrated that AS and IU can be considered psychobiological constructs that each uniquely relate to RDoC and HiTOP domains. When conducting research aimed at establishing psychobiological understanding, it is important to consider measurement error at the biological level and the increased likelihood of successful cross-unit integration with more proximal units of analysis. We propose an innovative, scientifically rigorous quantitative approach to integrate event-related potentials (ERPs; time-locked neural responding to cognitive-behavioral tasks) with self-reports of AS and IU. Specifically, confirmatory factor analysis (CFA) will be used to create psychoneurometric (PN) bifactor models of AS and IU. We further propose that these PN bifactor models will demonstrate unique relations with RDoC and HiTOP domains. Specific Aim 1 will validate PN bifactor models of AS and IU. It is posited that the PN bifactor solutions will fit the data better than uni- and multi-dimensional models (H1). AS and IU can be linked to RDoC constructs (acute threat and potential threat, respectively) and emotional distress clusters of disorders (fear- based and distress-based, respectively). Specific Aim 2 will demonstrate convergent and discriminant validity for the PN bifactor models of AS and IU with RDoC constructs and emotional distress disorder clusters. It is posited that the AS factors will be most related to acute threat and fear-based disorders and IU will be most related to potential threat and distress-based disorders (H2). The proposed project will 1) establish an approach for linking units of analysis consistent with a psychobiological model and 2) demonstrate convergent and discriminant validity for AS and IU in relation to the RDoC and HiTOP approaches, thus providing a bridge between the two systems of assessing psychopathology.